Effect of intracerebral hydroxytyrosol and its nitroderivatives on striatal dopamine metabolism: A study by in vivo microdialysis

AimsThe natural phenolic oil compound hydroxytyrosol (HTy) is widely studied because of its antioxidant and neuroprotective properties. Nitroderivatives of HTy have been studied in order to evaluate their putative effects on catechol-O-methyltransferase (COMT) activity.Main methodsTo study its effect on dopamine metabolism, nitrohydroxytyrosol and its lipophilic derivatives (nitrohydroxytyrosyl acetate and ethyl nitrohydroxytyrosyl ether), were administered into the rat corpus striatum through a microdialysis probe. Other catechols (HTy and the known COMT inhibitor Ro 41-0960) were also studied for comparison.Key findingsThe olive oil phenolic compounds (nitroderivatives and HTy) increased extracellular levels of 3,4-dihydroxyphenylacetic acid during the perfusion with similar maximum values to that of Ro 41-0960 when comparing to basal dialysate levels (approximately 140%). None of the compound series produced a decrease in the homovanillic acid extracellular levels below 75%. Among all novel compounds studied, both lipophilic nitrocatechols (nitrohydroxytyrosyl acetate and ethyl nitrohydroxytyrosyl ether) showed a long-acting effect over time once the perfusion through the microdialysis probe ended.SignificanceIn accordance with the actual design of novel COMT inhibitors with a long profile, our results suggest a certain influence of the side chain substituent on the COMT activity that could provide new lipophilic COMT inhibitors.